Diagnostic and prognostic significance of systemic alkyl quinolones for P. aeruginosa in cystic fibrosis: A longitudinal study

Abstract

BackgroundPulmonary P. aeruginosa infection is associated with poor outcomes in cystic fibrosis (CF) and early diagnosis is challenging, particularly in those who are unable to expectorate sputum. Specific P. aeruginosa 2-alkyl-4-quinolones are detectable in the sputum, plasma and urine of adults with CF, suggesting that they have potential as biomarkers for P. aeruginosa infection.AimTo investigate systemic 2-alkyl-4-quinolones as potential biomarkers for pulmonary P. aeruginosa infection.MethodsA multicentre observational study of 176 adults and 68 children with CF. Cross-sectionally, comparisons were made between current P. aeruginosa infection using six 2-alkyl-4-quinolones detected in sputum, plasma and urine against hospital microbiological culture results. All participants without P. aeruginosa infection at baseline were followed up for one year to determine if 2-alkyl-4-quinolones were early biomarkers of pulmonary P. aeruginosa infection.ResultsCross-sectional analysis: the most promising biomarker with the greatest diagnostic accuracy was 2-heptyl-4-hydroxyquinoline (HHQ). In adults, areas under the ROC curves (95% confidence intervals) for HHQ analyses were 0.82 (0.75–0.89) in sputum, 0.76 (0.69–0.82) in plasma and 0.82 (0.77–0.88) in urine. In children, the corresponding values for HHQ analyses were 0.88 (0.77–0.99) in plasma and 0.83 (0.68–0.97) in urine.Longitudinal analysis: Ten adults and six children had a new positive respiratory culture for P. aeruginosa in follow-up. A positive plasma HHQ test at baseline was significantly associated with a new positive culture for P. aeruginosa in both adults and children in follow-up (odds ratio (OR) = 6.67;-95% CI:-1.48–30.1;-p = 0.01 and OR = 70; 95% CI: 5–956;-p < 0.001 respectively).ConclusionsAQs measured in sputum, plasma and urine may be used to diagnose current infection with P. aeruginosa in adults and children with CF. These preliminary data show that plasma HHQ may have potential as an early biomarker of pulmonary P. aeruginosa. Further studies are necessary to evaluate if HHQ could be used in clinical practice to aid early diagnosis of P. aeruginosa infection in the future.

Micro-rheological properties of lung homogenates correlate with infection severity in a mouse model of Pseudomonas aeruginosa lung infection

“…To the best of our knowledge, this is the first time that a very strong correlation between PQS or HHQ and bacterial load in biological samples has been demonstrated. In two studies by Barr and coworkers 9,16 , the correlation of HHQ concentration in plasma samples from CF patients with bacterial load of sputum was significant in a moderate to weak range (r = 0.28 and r = 0.51) and in a study by Collier and coworkers, a correlation between PQS and bacterial density in sputum samples from CF patients was shown but not quantitatively 17 . Considering the mucoid feature of the P. aeruginosa NH57388A strain, we investigated whether the determined bacterial load and the detected signal molecule levels could further be correlated with the mechanical properties of the lung homogenate.…”

Metabolic Phenotyping and Strain Characterisation of Pseudomonas aeruginosa Isolates from Cystic Fibrosis Patients Using Rapid Evaporative Ionisation Mass Spectrometry

“…The detected metabolome may be further linked with clinical disease indicators such as the rate of disease progression or pulmonary exacerbations. Based upon the unique MS profile obtained with no sample extraction, it is plausible that the metabolites identified here can be detected in native samples such as sputum, and serve as universal chemical markers for culture-free diagnostic methods, using not only MS techniques 38 but also alternative methods such as semi-conductor or bio-sensors 39 . This would allow for an earlier detection of P .…”

Cytotoxic alkyl-quinolones mediate surface-induced virulence in Pseudomonas aeruginosa

“…Surface-induced virulence in P. aeruginosa reevaluation of the importance of AQs as direct cytotoxins in different animal infection models. Furthermore, given the chronic nature of many P. aeruginosa infections [2,35], and correlations between AQ levels and clinical progression [39,40], prolonged exposure to sub-μM levels of AQs could significantly impact tissue health over time.…”